Proteins and other molecules such as nucleic acids often have active sites that are capable of binding compounds of interest, or analytes, with great specificity. Highly selective biosensors having a protein, such as an enzyme, antibody, aptamer or other molecule, capable of selectively binding such analytes are known in the art. Some such sensors make use of a chemical reaction catalyzed by the protein as part of providing a detectable signal. In other sensors, such as surface plasmon sensors, binding of the compound of interest to the protein causes a physical change in a resonance that can be detected by suitable equipment.
It is known that small nanoparticles undergo a random motion induced by impact with randomly moving molecules called Brownian motion. Brownian motion can be detected and monitored with a technique called Magnetic Spectroscopy of Nanoparticle Brownian Motion (MSB), described in an article published as A. M. Rauwerdink, J. B. Weaver, “Measurement of Molecular Binding Using The Brownian Motion of Magnetic Nanoparticle Probes” Applied Physics Letters 96, 033702 (2010) and on the web in Feb. 1, 2010 issue of Virtual Journal of Biological Physics Research. The method also appears on the web at http://engineering.dartmouth.edu/reu/documents/CharlieTsai_FinalReport.pdf, and for which a copy is attached as an appendix hereto, the contents of which are incorporated herein by reference. It is also known that Brownian motion is a function of particle size, with larger, heavier, particles exhibiting smaller displacements than smaller, lighter, particles.
Magnetic nanoparticles, which typically have cores of either iron or iron oxide, have been coated with proteins or other molecules capable of selectively binding to analytes. When such particles are in suspension, a change in Brownian motion as measured by MSB can be detected when the particles are exposed to the analytes. Strong signal changes occur when multiple nanoparticles bind to the same analyte molecules and therefore agglutinate or aggregate—agglutinated nanoparticles effectively forming fewer but larger and heavier nanoparticles in the suspension; similar signal changes occur when the analyte binds nanoparticles to larger structures such large beads or the solid surfaces. However, changes also occur when individual molecules of analyte bind individual nanoparticles.